CA2078694C - Vaccin contre l'hepatite b - Google Patents
Vaccin contre l'hepatite bInfo
- Publication number
- CA2078694C CA2078694C CA002078694A CA2078694A CA2078694C CA 2078694 C CA2078694 C CA 2078694C CA 002078694 A CA002078694 A CA 002078694A CA 2078694 A CA2078694 A CA 2078694A CA 2078694 C CA2078694 C CA 2078694C
- Authority
- CA
- Canada
- Prior art keywords
- protein
- vhbsag
- fragment
- point mutation
- codon
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- SPSXSWRZQFPVTJ-ZQQKUFEYSA-N hepatitis b vaccine Chemical compound C([C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCSC)C(=O)N[C@@H](CC1N=CN=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)OC(=O)CNC(=O)CNC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](N)CCCNC(N)=N)C1=CC=CC=C1 SPSXSWRZQFPVTJ-ZQQKUFEYSA-N 0.000 title description 2
- 229940124736 hepatitis-B vaccine Drugs 0.000 title description 2
- 108090000623 proteins and genes Proteins 0.000 claims description 47
- 102000004169 proteins and genes Human genes 0.000 claims description 42
- 239000012634 fragment Substances 0.000 claims description 41
- 229960005486 vaccine Drugs 0.000 claims description 29
- 108091026890 Coding region Proteins 0.000 claims description 23
- 108020004705 Codon Proteins 0.000 claims description 23
- 230000035772 mutation Effects 0.000 claims description 21
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 20
- 239000004471 Glycine Substances 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 15
- 108020004414 DNA Proteins 0.000 claims description 14
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 14
- 150000001413 amino acids Chemical class 0.000 claims description 13
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 13
- 239000013598 vector Substances 0.000 claims description 13
- 208000002672 hepatitis B Diseases 0.000 claims description 10
- 239000004475 Arginine Substances 0.000 claims description 9
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 9
- 208000006454 hepatitis Diseases 0.000 claims description 9
- 231100000283 hepatitis Toxicity 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 239000013604 expression vector Substances 0.000 claims description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 4
- 239000010836 blood and blood product Substances 0.000 claims description 4
- 229940125691 blood product Drugs 0.000 claims description 4
- 238000001514 detection method Methods 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 3
- 125000000539 amino acid group Chemical group 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims description 3
- 238000003780 insertion Methods 0.000 claims description 2
- 230000037431 insertion Effects 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 238000011282 treatment Methods 0.000 claims description 2
- 238000003745 diagnosis Methods 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 241000700721 Hepatitis B virus Species 0.000 description 36
- 238000000034 method Methods 0.000 description 22
- 235000018102 proteins Nutrition 0.000 description 19
- 235000001014 amino acid Nutrition 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 101150010882 S gene Proteins 0.000 description 14
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 14
- 238000003752 polymerase chain reaction Methods 0.000 description 13
- 239000000427 antigen Substances 0.000 description 10
- 102000036639 antigens Human genes 0.000 description 10
- 108091007433 antigens Proteins 0.000 description 10
- 239000013612 plasmid Substances 0.000 description 8
- 239000011324 bead Substances 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 239000013615 primer Substances 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- 230000008859 change Effects 0.000 description 6
- 238000002649 immunization Methods 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 101710142246 External core antigen Proteins 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000002773 nucleotide Substances 0.000 description 5
- 125000003729 nucleotide group Chemical group 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 108020004511 Recombinant DNA Proteins 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000012163 sequencing technique Methods 0.000 description 4
- 239000007790 solid phase Substances 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- 108010054576 Deoxyribonuclease EcoRI Proteins 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 108010050151 hepatitis B hyperimmune globulin Proteins 0.000 description 3
- 230000002480 immunoprotective effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 102100031673 Corneodesmosin Human genes 0.000 description 2
- 101710139375 Corneodesmosin Proteins 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- 241000235058 Komagataella pastoris Species 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 241000320412 Ogataea angusta Species 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 101710136739 Teichoic acid poly(glycerol phosphate) polymerase Proteins 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 2
- 238000000137 annealing Methods 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 238000012411 cloning technique Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 230000004224 protection Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 210000002845 virion Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 210000005253 yeast cell Anatomy 0.000 description 2
- 241001076939 Artines Species 0.000 description 1
- 101000782236 Bothrops leucurus Thrombin-like enzyme leucurobin Proteins 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 241000905957 Channa melasoma Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 229940124884 Engerix-B Drugs 0.000 description 1
- 241001646716 Escherichia coli K-12 Species 0.000 description 1
- 108010026624 GTCGAC-specific type II deoxyribonucleases Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102100027377 HBS1-like protein Human genes 0.000 description 1
- 101001009070 Homo sapiens HBS1-like protein Proteins 0.000 description 1
- 101100514359 Mus musculus Mrtfa gene Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 101100226950 Pichia angusta FMDH gene Proteins 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 108020005038 Terminator Codon Proteins 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 241001105470 Valenzuela Species 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- 229940001007 aluminium phosphate Drugs 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000001483 arginine derivatives Chemical class 0.000 description 1
- 108010058966 bacteriophage T7 induced DNA polymerase Proteins 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 229940031416 bivalent vaccine Drugs 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 1
- SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 1
- RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 1
- HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 1
- NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000002998 immunogenetic effect Effects 0.000 description 1
- 230000017555 immunoglobulin mediated immune response Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 229940031348 multivalent vaccine Drugs 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000012798 spherical particle Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2730/00—Reverse transcribing DNA viruses
- C12N2730/00011—Details
- C12N2730/10011—Hepadnaviridae
- C12N2730/10111—Orthohepadnavirus, e.g. hepatitis B virus
- C12N2730/10122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Variant de la protéine HBsAg ou fragment dudit variant affichant l'antigénicité de l'antigène de surface du virus de l'hépatite B. Le variant ou son fragment (vHBsAg) comprend un déterminant 'a' modifié comprenant un acide aminé autre que la glycine en position 145 de la séquence de HBsAg. Un vaccin comprenant vHBsAg est fourni, tout comme une trousse pour la détection diagnostique in vitro des anticorps anti-vHBsAg et une préparation d'anticorps comprenant des anticorps anti-vHBsAg.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB909007024A GB9007024D0 (en) | 1990-03-29 | 1990-03-29 | Novel vaccine |
| GB9007024.4 | 1990-03-29 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2078694A1 CA2078694A1 (fr) | 1991-09-30 |
| CA2078694C true CA2078694C (fr) | 1998-10-27 |
Family
ID=10673467
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002078694A Expired - Fee Related CA2078694C (fr) | 1990-03-29 | 1991-03-25 | Vaccin contre l'hepatite b |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US6099840A (fr) |
| EP (1) | EP0522030B1 (fr) |
| JP (2) | JP2876091B2 (fr) |
| KR (1) | KR100208129B1 (fr) |
| AT (1) | ATE125821T1 (fr) |
| CA (1) | CA2078694C (fr) |
| DE (1) | DE69111801T2 (fr) |
| DK (1) | DK0522030T3 (fr) |
| ES (1) | ES2075440T3 (fr) |
| GB (1) | GB9007024D0 (fr) |
| GR (1) | GR3017804T3 (fr) |
| IE (1) | IE67877B1 (fr) |
| NZ (1) | NZ237611A (fr) |
| PT (1) | PT97159B (fr) |
| WO (1) | WO1991014703A1 (fr) |
| ZA (1) | ZA912305B (fr) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5565354A (en) * | 1986-09-05 | 1996-10-15 | Sandoz Ltd. | Production of human monoclonal antibodies specific for hepatitis B surface antigen |
| CA2067003A1 (fr) * | 1991-04-29 | 1992-10-30 | Peter J. Kniskern | Vaccin mutant de variante d'antigene de surface d'hbv |
| EP0533263A3 (en) * | 1991-09-20 | 1994-06-08 | Merck & Co Inc | A multivalent hepatitis b virus vaccine |
| WO1993012815A1 (fr) * | 1991-12-27 | 1993-07-08 | Gensci Limited | Procede d'obtention d'un antigene de surface recombine de l'hepatite b, antigene et vaccin a base de celui-ci |
| EP0565794A1 (fr) * | 1992-04-14 | 1993-10-20 | British Biotech Pharmaceuticals Limited | Induction des réponses CTL |
| DE69319728T2 (de) | 1992-05-23 | 1999-02-04 | Smithkline Beecham Biologicals S.A., Rixensart | Kombinierte Impfstoffe, die Hepatitis B oberfläche Antigen und andere Antigenen enthalten |
| US5750106A (en) * | 1993-01-28 | 1998-05-12 | Novartis Ag | Human monoclonal antibodies to cytomegalovirus |
| CA2158866A1 (fr) * | 1993-03-24 | 1994-09-29 | Jennifer Anne Waters | Molecules liantes specifiques d'un mutant du gene de l'hepatite b |
| US6030616A (en) * | 1993-03-24 | 2000-02-29 | Imperial College Of Science, Technology & Medicine | Hepatitis B escape mutant specific binding molecules |
| US5595739A (en) * | 1993-05-07 | 1997-01-21 | Abbott Laboratories | Hepatitis B virus mutants, reagents and methods for detection |
| GB9401987D0 (en) * | 1994-02-02 | 1994-03-30 | Imperial College | Modified nucleic acid |
| GB9623233D0 (en) | 1996-11-07 | 1997-01-08 | Smithkline Beecham Biolog | Vaccine composition |
| EP0919568A1 (fr) | 1997-12-01 | 1999-06-02 | Sorin Diagnostics S.r.l. | Mutants de fuite des antigènes de surface du virus de l'hépatite B |
| HUP0103258A3 (en) * | 1998-06-19 | 2003-10-28 | Government Of The Republic Of | A vaccine-induced hepatitis b viral strain and uses thereof |
| AU750587B2 (en) | 1998-10-16 | 2002-07-25 | Smithkline Beecham Biologicals (Sa) | Adjuvant systems and vaccines |
| AUPP967999A0 (en) | 1999-04-09 | 1999-05-06 | North Western Health Care Network | Viral variants |
| UA79735C2 (uk) | 2000-08-10 | 2007-07-25 | Глаксосмітклайн Байолоджікалз С.А. | Очищення антигенів вірусу гепатиту b (hbv) для використання у вакцинах |
| FR2815634B1 (fr) * | 2000-10-20 | 2003-10-31 | Biomerieux Sa | Anticorps monoclonaux diriges contre des virus de l'hepatite b |
| CA2580620C (fr) | 2004-09-22 | 2014-04-22 | Advanced Life Science Institute, Inc. | Methode de detection de l'antigene s du virus de l'hepatite b |
| BRPI0610297A2 (pt) * | 2005-04-18 | 2010-06-08 | Novartis Vaccines & Diagnostic | expressão de antìgeno de superfìcie de vìrus da hepatite b para a preparação de vacina |
| GB0514578D0 (en) | 2005-07-15 | 2005-08-24 | Orthotics Online Ltd | Copper orthotic |
| EP2207035B1 (fr) | 2006-03-14 | 2013-10-16 | Oregon Health and Science University | Procédés pour détecter une infection de tuberculose à mycobactérie |
| EA015964B1 (ru) | 2006-09-07 | 2012-01-30 | Глаксосмитклайн Байолоджикалс С.А. | Вакцина |
| WO2008106551A2 (fr) | 2007-02-28 | 2008-09-04 | The Govt. Of The U.S.A. As Represented By The Secretary Of The Dept. Of Health & Human Serv. | Polypeptides brachyury et procédés d'utilisation. |
| EA201490303A1 (ru) | 2007-05-02 | 2014-05-30 | Глаксосмитклайн Байолоджикалс С.А. | Вакцина |
| WO2009143524A2 (fr) | 2008-05-23 | 2009-11-26 | The Regents Of The University Of Michigan | Vaccins à nanoémulsion |
| WO2010099472A2 (fr) | 2009-02-27 | 2010-09-02 | The U.S.A. Of America, As Represented By The Secretary, Department Of Health And Human Services | Polypeptides spanx-b et leur utilisation |
| GB201105981D0 (en) | 2011-04-08 | 2011-05-18 | Glaxosmithkline Biolog Sa | Novel process |
| ES2712686T3 (es) | 2012-07-10 | 2019-05-14 | Green Cross Corp | Una composición de anticuerpos para la prevención o el tratamiento de una infección por un virus de la hepatitis B mutante |
| ES2752190T3 (es) | 2012-09-14 | 2020-04-03 | Us Health | Proteína Brachyury, vectores adenovirales que codifican proteína Brachyury y su uso |
| RU2603729C2 (ru) * | 2015-04-24 | 2016-11-27 | Закрытое акционерное общество научно-производственная компания "Комбиотех" | Рекомбинантная вакцина для профилактики вирусного гепатита в (варианты) |
| RU2586513C1 (ru) * | 2015-04-24 | 2016-06-10 | Закрытое акционерное общество научно-производственная компания "Комбиотех" | РЕКОМБИНАНТНЫЙ ШТАММ ДРОЖЖЕЙ Hansenula polymorpha - ПРОДУЦЕНТ МУТАНТНОГО ПОВЕРХНОСТНОГО АНТИГЕНА ВИРУСА ГЕПАТИТА В (ВАРИАНТЫ) |
| EP4137150A1 (fr) | 2015-08-03 | 2023-02-22 | The United States of America, as represented by the Secretary, Department of Health and Human Services | Mutants de délétion de la protéine brachyury, vecteurs sans levure codant pour les mutants de délétion de la protéine brachyury, et leur utilisation |
-
1990
- 1990-03-29 GB GB909007024A patent/GB9007024D0/en active Pending
-
1991
- 1991-03-25 EP EP91907263A patent/EP0522030B1/fr not_active Expired - Lifetime
- 1991-03-25 CA CA002078694A patent/CA2078694C/fr not_active Expired - Fee Related
- 1991-03-25 AT AT91907263T patent/ATE125821T1/de not_active IP Right Cessation
- 1991-03-25 KR KR1019920702341A patent/KR100208129B1/ko not_active Expired - Fee Related
- 1991-03-25 DK DK91907263.7T patent/DK0522030T3/da active
- 1991-03-25 DE DE69111801T patent/DE69111801T2/de not_active Expired - Fee Related
- 1991-03-25 ES ES91907263T patent/ES2075440T3/es not_active Expired - Lifetime
- 1991-03-25 WO PCT/GB1991/000444 patent/WO1991014703A1/fr not_active Ceased
- 1991-03-25 JP JP3506486A patent/JP2876091B2/ja not_active Expired - Fee Related
- 1991-03-27 IE IE102291A patent/IE67877B1/en not_active IP Right Cessation
- 1991-03-27 PT PT97159A patent/PT97159B/pt not_active IP Right Cessation
- 1991-03-27 NZ NZ237611A patent/NZ237611A/xx unknown
- 1991-03-27 ZA ZA912305A patent/ZA912305B/xx unknown
-
1995
- 1995-06-07 US US08/479,609 patent/US6099840A/en not_active Expired - Fee Related
- 1995-10-18 GR GR950402907T patent/GR3017804T3/el unknown
-
1998
- 1998-09-24 JP JP10269188A patent/JP3049018B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP0522030A1 (fr) | 1993-01-13 |
| GB9007024D0 (en) | 1990-05-30 |
| ATE125821T1 (de) | 1995-08-15 |
| JP3049018B2 (ja) | 2000-06-05 |
| ES2075440T3 (es) | 1995-10-01 |
| ZA912305B (en) | 1992-01-29 |
| JPH11178591A (ja) | 1999-07-06 |
| AU7561391A (en) | 1991-10-21 |
| EP0522030B1 (fr) | 1995-08-02 |
| NZ237611A (en) | 1994-09-27 |
| DE69111801T2 (de) | 1995-12-14 |
| PT97159B (pt) | 1998-07-31 |
| JPH05505805A (ja) | 1993-08-26 |
| DK0522030T3 (da) | 1995-12-27 |
| CA2078694A1 (fr) | 1991-09-30 |
| GR3017804T3 (en) | 1996-01-31 |
| JP2876091B2 (ja) | 1999-03-31 |
| US6099840A (en) | 2000-08-08 |
| IE67877B1 (en) | 1996-05-01 |
| DE69111801D1 (de) | 1995-09-07 |
| AU642729B2 (en) | 1993-10-28 |
| IE911022A1 (en) | 1991-10-09 |
| WO1991014703A1 (fr) | 1991-10-03 |
| KR100208129B1 (ko) | 1999-07-15 |
| PT97159A (pt) | 1991-12-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0522030B1 (fr) | Vaccin de l'hepatite b | |
| EP0563093B1 (fr) | Composition utilisee comme agent therapeutique contre des maladies hepatiques virales chroniques | |
| US5856084A (en) | Hepatitis B vaccine | |
| IE902690A1 (en) | Novel antigens and methods therefor | |
| US5639637A (en) | Hepatitis B vaccine | |
| IE60387B1 (en) | Hepatitis B virus vaccine | |
| US6103519A (en) | Antigens and methods therefor | |
| KR100637282B1 (ko) | Ｂ형 간염 바이러스 폴리펩티드 | |
| AU642729C (en) | Hepatitis B vaccine | |
| US5989865A (en) | Hepatitis B vaccine | |
| Tron | Hepatitis B virus recombinant vaccines: achievement and progress | |
| Schodel | Hepatitis B virus vaccines | |
| CA2078358A1 (fr) | Vaccin multivalent contre le virus de l'hepatite b | |
| HOWARD et al. | Hepatitis Β Virus: Approaches to Control and Vaccination | |
| HK1002901B (en) | A composition used as a therapeutic agent against chronic viral hepatic diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |